Compliance, adverse events and quality of life of patients in a phase 3 study comparing temozolomide with PCV as adjuvant chemotherapy in grade 2 and 3 glioma.
Authors: Nandini Sharrel Menon, Tejpal Gupta, Abhishek Chatterjee, Amit Choudhary, Ameya Puranik, Epari Sridhar, Archya Dasgupta, Ayushi Sahay, Aliasgar Moiyadi, Prakash Shetty, Vikas Kumar Singh, Shruti Pathak, Naveen Karuvandan, Zoya Peelay, Hemanth Kumar, Madala Ravi Krishna, Monica Jadhav, Rakesh Jalali, Vijay Maruti Patil
Journal: Journal of Clinical Oncology (2022)

e14010 Background: Both PCV and Temozolomide (TMZ) are options for adjuvant therapy in grade 2 &amp; grade 3 gliomas after maximal safe resection. The RTOG 9802 PCV regimen is not commonly used as it is perceived as a toxic, poorly tolerated regimen. TMZ is often preferred as it is easy to administer and has fewer adverse events. There has been no head-to-head comparison of these regimens, hence we are conducting a study to compare the 2 regimens. Here, we report the adverse event profile, compliance &amp; quality of life (QoL) of patients enrolled in this study. Methods: This is an ongoing phase 3, non-inferiority trial. Adults with grade 2 glioma with high-risk features (age ≥40 years at diagnosis or residual disease ≥1 cm) or grade 3 gliomas, with ECOG PS 0-2 were enrolled. Patients were randomized 2:1 to receive either adjuvant TMZ or PCV after adjuvant focal conformal radiation (RT). In the TMZ arm patients received RT with concurrent TMZ 75 mg/m2/day (max. 49 days) followed by adjuvant TMZ 150 mg/m2/day on days 1-5 of a 28 day cycle for cycle1, &amp; 200 mg/m2/day cycle 2 onwards (max. 12 cycles).In the PCV arm, patients received Procarbazine 60 mg/m2/day on days 8-21, Lomustine (CCNU) 110 mg/m2 on day 1 &amp; Vincristine (VCR) 1.4 mg/m2 on days 8 &amp; 29 of a 56 day cycle (max. 6 cycles). The primary endpoint of the study is progression-free survival. The current analysis focuses on compliance, adverse events (as per CTCAE v4.03) &amp; QoL (EORTC QLQ C-30 &amp; BN-20). Results: This analysis was limited to the first 50 patients who had completed at least 1 year from the start of adjuvant chemotherapy. There were 32 patients in the TMZ arm &amp; 18 patients in the PCV arm. Two patients each in the TMZ &amp; PCV arms did not start adjuvant chemotherapy. Among those who started adjuvant chemotherapy, the completion rates were higher in the TMZ arm (n = 26,86.7%) as compared to the PCV arm (n = 11,68.8%; p = .241). The median number of cycles of TMZ, Procarbazine, CCNU, and VCR were 12, 5.5, 6 and 5.5 respectively. Dose delays were slightly higher in the PCV arm (81.3%) compared to the TMZ arm (73.3%) which was not statistically significant (p = .722). Chemotherapy dose reductions were needed in 11 patients (68.8%) in the PCV arm &amp; only 1 patient (3.3%) in the TMZ arm, this was statistically significant (p = 0.000). Myelosuppression was significantly higher in the PCV arm as compared to the TMZ arm. The incidence of any grade and grade ≥ 3 anemia, neutropenia &amp; thrombocytopenia was significantly higher with PCV. The incidence of grade 3 lymphopenia was significantly higher with PCV (p = .000). Only 2 patients in the PCV arm developed febrile neutropenia. There was no significant difference in the QoL scores between the two arms at various time points. Conclusions: The use of adjuvant PCV is feasible when administered by experienced neuro-medical oncologists with an acceptable compliance and toxicity profile, without adversely impacting the QoL of patients. Clinical trial information: CTRI/2018/07/015056.